However, a recent study reported no changes in the methylation of 5′ region of the RELN promoter [40] compared to nAD cases, although DNA-methyltransferase 1 (the main enzyme responsible for the hypomethylation of RELN promoter) is downregulated in AD brains and RELN mRNA levels are higher than nND in the study. The gene discussed is RELN; the disease is Alzheimer disease.